Peptaibol metabolites of Tolypocladium geodes

Abstract

Three antibiotic peptides, LP237-F8 (1), F5 (2), and F7 (3), were isolated from the liquid culture of the fungus Tolypocladium geodes. Chemical shift assignments of the 1H and 13C NMR resonances and sequencing of these metabolites were achieved by extensive high-field 2D NMR spectroscopy. The N-terminal of peptides 1 and 2 is protected with an octanoyl (Oc) fatty acid unit, whereas that of peptide 3 is protected with a decanoyl (Dec) unit. The C-terminal of all three peptides is protected with the amino alcohol leucinol (Lol). All three metabolites contain the common amino acids Ala, Phe or Tyr, Pro, and Gln, as well as the unusual amino acid α-aminoisobutyric acid (Aib). In addition, peptides 1 and 2 contain the amino acid α-amino-α-ethyl-n-pentanoic acid (α-ethylnorvaline, EtNor), which has not been previously reported as a constituent of a natural product. Metabolites 1, 2, and 3 are new members of the class of natural products known as peptaibols. Key words: Tolypocladium geodes, peptaibols, leucinol, α-amino-α-ethyl-n-pentanoic acid.